Polymeric sealant for use in mammals (as amended)

ABSTRACT

The invention provides a polymeric medical sealant for use in mammals other than humans. The medical sealant is useful for application to the tonsils, adenoids or paranasal sinus, wherein the sealant performs at least one of the following functions, a) inhibit the colonization of bacteria, b) inhibit the binding of bacteria to tissue, c) reduction of tissue morbidity, d) hemostasis, e) coating and protection of tissue during healing, f) promotion of healing, and g) reduction of pain.

CROSS REFERENCE TO RELATED APPLICATION

This application is a Divisional of U.S. application Ser. No.11/704,115, filed Feb. 8, 2007, the disclosure of which is incorporatedherein by reference.

THE FIELD OF THE INVENTION

The present invention relates generally to the field of film-formingmedical compositions, more specifically to methods and products used toseal mucosa, lessen pain and facilitate recovery by application of apolymeric sealant composition for use in bodily tissues, such astreatment of the throat, tonsils and/or adenoids.

BACKGROUND OF THE INVENTION

Adenoids (pharyngeal tonsils) and tonsils (palatine tonsils) areinvolved in a number of diseases of the ear, nose, and throat includingchronic otitis media with effusion (COME), recurrent acute otitis media(RAOM), adenoiditis, pediatric chronic sinusitis, tonsillitis, pediatricobstructive sleep apnea (OSA), adult OSA, and chronic strep throat.Lingual tonsils can also become infected and be problematic. Treatmentfor these diseases is primarily achieved first by use of oralmedications or, in the case of pediatric and adult sleep apnea throughthe use of continuous positive airway pressure (CPAP). Otitis media ismost often treated primarily with ventilation tube surgery. Failure ofthese therapies is often followed by surgical removal of the tonsilsand/or adenoids to remove them either because they are a harbor forbacteria or as obstructing anatomy. Complications related to theseprocedures include post-operative bleeding, dehydration, weight loss,peritonsillar abscess, torticilis (neck stiffness), regrowth of tissue,redo surgery due to incomplete removal of tissue, continued COME orRAOM, continued OSA, and occasionally death. Post-operative treatmenthas traditionally been limited to dietary limitation, rinses, and use oforal antibiotics to prevent post-operative pain and infections.

It has now been discovered that a polymeric film-forming medical sealantcomposition may be applied to the throat to provide multiple treatmentand/or prophylactic functions such as reduction of bleeding, preventionof post-operative infections, tissue protection, reduction in pain, andthe like. It is also anticipated that such sealant could be used in thethroat, especially on the tonsils, adenoids or the post-operativeadenoid remnant to treat otitis media, given the involvement in thedisease.

Useful polymeric film-forming medical sealants of the invention may beapplied directly to the affected area, are generally resorbablematerials which may have residence times of one day or many days orweeks.

SUMMARY OF THE INVENTION

The invention provides a polymeric film-forming sealant for use inmedical applications.

Specifically, the invention provides a polymeric film-forming sealantwhich is useful in applications for treatment and/or post-operative careof the tonsils and adenoids.

More specifically, the invention provides a polymeric film-formingmedical sealant useful for application to the tonsils and adenoids,wherein the sealant performs at least one of the following functions, a)inhibits the colonization of bacteria, b) inhibits the binding ofbacteria to tissue, c) reduction of tissue morbidity, d) hemostasis, e)coating and protection of tissue during healing, especiallypostoperative healing, and f) delivery of therapeutic agent(s). In oneembodiment, the application of the polymeric sealant of the inventionalso reduces pain in tissue to which it is applied during treatment orpostoperative healing. In another embodiment, the application of thepolymeric sealant of the invention also reduces bleeding in tissue towhich it is applied.

The polymeric film-forming medical sealant of the invention may furtherbe comprised of a natural therapeutic material such as chitosan, etc. orinclude at least one therapeutic agent. In one embodiment, the sealantfurther includes a therapeutic agent selected from the group consistingof analgesics, antihistamines, anti-infective agents, anti-bacteriaadhesion agents, anti-fungal agents, biostatic compositions,anti-inflammatory agents, anti-cholinergics, anti-neoplastic agents,cytokines, decongestants, vitamins, peptides, proteins, nucleic acids,immunosuppressors, vasoconstrictors, and mixtures thereof.

The polymeric sealant of the invention may be a viscoelastic material.In another embodiment, the polymeric sealant of the invention may hardenafter application. In most embodiments, the sealant is a resorbablematerial having a residence time in vivo of from one day to weeks ormonths.

The invention also provides a method of treatment for maladies orchronic conditions of the tonsils or adenoids which comprises the stepof providing at least one polymeric film-forming medical sealant, andapplying it to the tonsils, adenoids or adjacent tissue. The inventionfurther provides a method of postoperative treatment for use afterremoval of the tonsils or adenoids which comprises the step of providingleast one polymeric film-forming medical sealant, and applying it to thethroat, such as to tonsillar fossa.

These terms when used herein have the following meanings:

1. The term “bioresorbable” as used herein, means capable of beingabsorbed by the body.

2. The term “hemostat” means a device or material which stops bloodflow.

3. The term “adhesion” as used herein, refers to the sticking togetherof a material to tissues with which it is in intimate contact forextended periods.

4. The term “residence time” means the time which the sealant remains inplace in vivo.

5. The term “polymeric sealant” means that the sealant is either formedfrom a synthetic polymer or is a natural polymeric material such as aprotein, which is crosslinked.

6. The term “biodegradable” means that the substance will degrade orerode in vivo to form smaller chemical species. Such degradation processmay be enzymatic, chemical or physical.

7. The term “biocompatible” means that the substance presents nosignificant deleterious or untoward effects upon the body.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The following detailed description describes certain embodiments and isnot to be taken in a limiting sense. The scope of the present inventionis defined by the appended claims.

The polymeric medical sealant provided herein may be used in any mannerin which will promote therapeutic improvement. Such uses include, butare not limited to wound management, tissue protection, reduction orelimination of bleeding, reduction of pain, promotion of healing,prevention of infection, and the like. The sealants may also be used assingle or combination drug delivery systems for humans or mammals.

The sealant of the invention is a biocompatible composition whichadheres to bodily tissues. Most useful sealants are resorbable ordegradable, as a non-resorbable or non-degradable adhesive or sealantcannot be used where damaged tissues are not meant to grow together as apermanent or semi-permanent barrier is created if the sealant is notresorbed or degraded.

In one embodiment the sealant may be a polymeric polymer such as silk orsilk-elastin polymers which are crosslinked just prior to delivery whichcan then be sprayed onto the tissue. Useful biodegradable polymers aridoligomers include, but are not limited to: poly(lactides),poly(glycolides), poly(lactide-co-glycolides), poly(lactic acids),poly(glycolic acids), polycaprolactones, polyamides, poly(malic acids),polyanhydrides, polyamino acids, polyorthoesters, polyetheresters,polycyanoacrylates, polyphosphazines, polyphosphoesters,polyesteramides, polydiozanones, polyacetals, polyketals,polycarbonates, degradable polyurethanes, polyvinyl pyrrolidones,polyhydroxybutyrates, polyhydoxyvalerates, polyalkylene oxalates,polyalkylene succinates, chitins, chitosans, oxidized celluloses,carboxymethylcellulose, gelatin, agar, and copolymers, terpolymers,blends, and mixtures thereof.

Useful crosslinking materials include, but are not limited to,polyethylene glycol (PEG), chitin, carboxymethylcellulose, and the like,carbodiimides, diisocyanates and/or aldehydes; such as glutaraldehyde orformaldehyde. The material cures to form a hydrogel, which stronglyadheres to the tissue.

In another embodiment, the sealant may be a natural protein such ascollagen or albumin which is crosslinked, most typically with aldehydes,such as glutaraldehyde or formaldehyde.

In yet another embodiment, the sealant may include a glycol along with anatural protein such as chitin, collagen, agar or albumin. The glycolmay be a material such as a polyethylene glycol.

The sealant of the invention may be applied in any known form, such as agel, one or more flowable liquids that crosslink, polymerize orotherwise alter their consistency to form a sealant, a film strip orsheet material, as a sponge, or as a powder which forms into a sealantor in atomized form may be sprayed onto the tissue.

The polymeric film-forming medical sealants useful for application tothe tonsils and adenoids perform at least one of the followingfunctions, a) inhibit the colonization of bacteria, b) inhibit thebinding of bacteria to tissue, c) reduction of tissue morbidity, d)hemostasis, e) coating and protection of tissue during healing, f)promotion of healing, and g) reduction of pain. In surgicalapplications, they may also reduce the formation of post-operativeperi-tonsillar abscess formation by reduction of infection and biofilmformation due to the protection of the tissues, and/or inclusion ofanti-infective agents. Healing is promoted through wound closure, andmaintenance of the wound as a moist wound, which promotes plateletaggregation, and wound closure without excessive scabrous formations,which occur in drier wounds. Acceleration of wound healing andprotection of the wound also reduce the chances of infection at thewound site, and resultant pain, inflammation and malodor.

The polymeric film-forming medical sealant may be comprised of a naturaltherapeutic biomaterial or may include one or more therapeutic agents.The therapeutic agent that may be added to the sealant is not limited innature, and any agent which is appropriate for medical use may be used.Some common therapeutic agents are those selected from the groupconsisting of analgesics, antihistamines, anti-infective agents such asanti-bacterial and anti-fungal agents, biostatic compositions,anti-inflammatory agents, anti-cholinergics, anti-neoplastic agents,cytokines, decongestants, vitamins, peptides, proteins, nucleic acids,vasoconstrictors and mixtures thereof.

Examples of useful additional therapeutic agents include but are notlimited to those listed herein. Some useful antibacterial agents includeaminoglycosides, amphenicols, ansamycins, beta-lactams such aspenicillins, ampicillins, cephalosporins, lincosamides, macrolides,nitrofurans, quinolines, sulfonamides, sulfones, tetracyclineantibiotics such as chlortricycline, oxytetracycline, demecocycline,doxycycline, democycline, minocycline, methocycline, mecoclycline,methacycline, lymecycline, and the like, vancomycin, and derivativesthereof and mixtures thereof. Examples of anti-fungals includeallylamines, imidazoles, polyenes, thiocarbamates, triazoles, andderivatives thereof. Anti-parasitic agents include atovaquone,clindamycin and the like.

In one embodiment, the tetracycline family of materials is preferredtherapeutic agents for their combination of anti-inflammatory propertiesand anti-infective properties. β-lactams that may be suitable for usewith the described methods and devices include, but are not limited to,carbacephems, carbapenems, cephalosporins, cephamycins, monobactams,oxacephems, penicillins, and any of their derivatives. Penicillins thatmay be suitable for use include, but are not limited to, amdinocillin,amdinocillin pivoxil, amoxicillin ampicillin, apalcillin, aspoxicillin,axidocillin, azlocillin, acampicillin, bacampicillin, benzylpenicillinicacid, benzylpenicillin sodium, carbenicillin, carindacillin,clometocillin, cloxacillin, cyclacillin, dicloxacillin, epicillin,fenbenicillin, floxacillin, hetacillin, lenampicillin, metampicillin,methicillin sodium, mezlocillin, nafcillin sodium, oxacillin,penamecillin, penethamate hydriodide, penicillin G benethamine,penicillin G benzathine, penicillin G benzhydrylamine, penicillin Gcalcium, penicillin G hydrabamine, penicillin G potassium, penicillin G.procaine, penicillin N, penicillin O, penicillin V, penicillin Vbanzathine, penicillin V hydrabamine, penimepicycline, phenethicillinpotassium, piperacillin, pivampicillin propicillin, quinacillin,sulbenicillin, sultamicillin, talampicillin, temocillin, andticarcillin. In one variation, amoxicillin may be included in theparanasal sinus device. In another variation, the additional agentincludes ampicillin. Penicillins combined with clavulanic aid such asAugmentin® (amoxicillin and clavulanic acid) may also be used.

Examples of antifungal agents suitable for use include, but are notlimited to, allylamines, imidazoles, polyenes, thiocarbamates,triazoles, and any of their derivatives. In one variation, imidazolesare the preferred antifungal agents. Anti-parasitic agents that may beemployed include such agents as atovaquone clindamycin, dapsone,iodoquinol, metronidazle, pentamidine, primaquine, pyrimethamine,sulfadiazine, trimethoprim/sufamethoxazole, trimetrexate, andcombinations thereof.

Examples of antiviral agents suitable for use include, but are notlimited to acyclovir, famciclovir, valacyclovir, edoxudine, ganciclovir,foscamet, cidovir (vistide), vitrasert, formivirsen, HPMPA(9-(3-hydroxy-2-phosphonomethoxypropyl)adenine), PMEA(9-(2-phosphonomethoxyethyl)adenine), HPMPG(9-(3-Hydroxy-2-(Phosphonomethoxy)propyl)guanine), PMEG(9-[2-(phosphonomethoxy)ethyl]guanine), HPMPC (1-(2-phosphonomethoxy-3-hydroxypropyl)-cytosine), ribavirin, EICAR(5-ethynl-1-beta-D-ribofuranosylimidazole-4-carbonxamine), pyrazofurin(3-[beta-D-ribofuranosyl]-4-hydroxypyrazole-5-carboxamine),3-Deazaguanine, GR-92938X(1-beta-D-ribofuranosylpyrazole-3,4-dicarboxamide), LY253963(1,34-thiadiazol-2-yl-cyanamide), RD3-0028(1,4-dihydro-2,3-Benzodithiin), CL387626(4,4′-bis[4,6-d][3-aminophenyl-N-N-bis(2-carbamoylethyl)-sulfonilimino]-1,3,5-triazin-2-ylamino-biphenyl-2-,2′-disulfonicacid disodium salt), BABIM (Bis[5-Amidino-2-benzimidazoly-1]-methane),NIH351, and combinations thereof.

Examples of steroidal anti-inflammatory agents that may be used in thedevices include 21-acetoxypregnenolone, alclometasone, algestone,amcinonide, beclomethasone, betamethasone, budesonide, chloroprednisone,clobetasol, clobetansone, clocortolone, cloprednol, corticosterone,cortisone, cortivazol, deflazacort, desonide, desoximetasone,dexamethasone, diflorasone, diflucortolone, difluprednate, enoxolone,fluazacort, flucloronide, flumethasone flunisolide, fluocinoloneacetonide, fluocinonide, fluocortin butyl, fluocortolone,fluorometholone, fluperolone acetate, fluprednidene acetate,fluprednisolone, flurandrenolide, fluticasone propionate, formocortal,halcinonide, halobetasol propionate, halometasone, halopredone acetate,hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone,medrysone, meprednisone, methylprednisolone, mometasone furoate,paramethosone, prednicarbate, prednisolone, prednisolone25-diethylamino-acetate, prednisolone sodium phosphate, prednisone,prednival, prednylidene, rimexolone, tixocortol, triamcinolone,triamcinolone acetonide, triamcinolone benetonide, triamcinolonehexacetonide, any of their derivatives, and combinations thereof. In onevariation, budesonide is included in the device as the steroidalanti-inflammatory agent. In another variation the steroidalanti-inflammatory agent may be mometasonefuroate. In yet anothervariation, the steroidal anti-inflammatory agent may be beclomethasone.In yet a further variation, the steroidal anti-inflammatory agent may befluticasone propionate.

Suitable nonsteroidal anti-inflammatory agents include, but are notlimited to, COX inhibitors (COX-1 or COX nonspecific inhibitors) (e.g.,salicylic acid derivatives, aspirin, sodium salicylate, cholinemagnesium trisalicylate, salicylate, diflunisal, sulfasalazine andolsalazine; para-aminophenol derivatives such as acetaminophen; indoleand indene acetic acids such as indomethacin and sulindac; heteroarylacetic acids such as tolmetin, dicofenac and ketorolac; arylpropionicacids such as ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofenand oxaprozin; anthranilic acids (fenamates) such as mefenamic acid andmeloxicam; enolic acids such as the oxicams (piroxicam, meloxicam) andalkanones such as nabumetone) and selective COX-2 inhibitors (e.g.,diaryl-substituted furanones such as refecoxib; diaryl-substitutedpyrazoles such as celecoxib; indole acetic acids such as etodolac andsulfonanilides such as nimesulide).

The chemotherapeutic/antineoplastic agents that may be used include, butare not limited to antitumor agents (e.g., cancer chemotherapeuticagents, biological response modifiers vascularization inhibitors,hormone receptor blocks, cryotherapeutic agents or other agents thatdestroy or inhibit neoplasia or tumorigenesis) such as alkylating agentsor other agents which directly kill cancer cells by attacking their DNA(e.g., cyclophosphamide, isophosphamide) nitrosoureas or other agentswhich kill cancer cells by inhibiting changes necessary for cellular DNArepair (e.g., carmustine (BCNU) and lomustine (CCNU)), antimetabolitesand other agents that block cancer cell growth by interfering withcertain cell functions, usually DNA synthesis (e.g., 6 mercaptopurineand 5-fluorouracil (5FU)), antitumor antibiotics and other compoundsthat act by binding or intercalating DNA and preventing RNA synthesis(e.g., doxorubicin, daunorubicin, epirubicin, idarubicin, mitomycin-Cand bleomycn) plant (vinca) alkaloids and other anti-tumor agentsderived from plants (e.g, vincristine and vinblastine), steroidhormones, hormone inhibitors, hormone receptor antagonists and otheragents which affect the growth of hormone-responsive cancers (e.g.,tamoxifen, herceptin, aromatase inhibitors such as aminoglutethamide,and formestane, triazole inhibitors such as letrozole and anastrazole,steroidal inhibitors such as exemastane) antiangiogenic proteins, smallmolecules, gene therapies and/or other agents that inhibit angiogenesisor vascularization of tumors (e.g., meth-1, meth-2, thalidomide),bevacizumab (Avastin) squalamine, endostatin, angiostatin, Angiozyme,AE-941 (Neoastat), CC-5013 (Revimid), medi-522 (Vitaxin),2-methoxyestradiol (2ME2, Panzem) carboxyamidotriazole (CAI)combretastatin A4 prodrug (CA4P), SU6668, SU11248, BMS-275291, COL-3,EMD 121974, IMC-1C11, IM862, TNP-470, celecoxib (Celebrex), refecoxib(Vioxx), interferon alpha, interleukin-12 (IL-12) or any of thecompounds identified in Science Vol. 298, Pages 1197-1201 (Aug. 17,2000), which is expressly incorporated herein by reference, biologicalresponse modifiers (e.g., interferon, bacillus calmette-guerin (BCG),monoclonal antibodies, interleuken 2, granulocyte colony stimulatingfactor (GCSF), etc.), PGDF receptor antagonists, herceptin,asparaginase, busulphan, carboplatin, cisplatin, carmustine,chlorambucil, cytarabine, dacarbazine, etoposide, flucarbazine,flurouracil, gemcitabine, hydroxyurea, ifosphamide, irinotecan,lomustine, melphalan, mercaptopurine, methotrexate, thioguanine,thiotepa, tomudex, topotecan, treosulfan, vinblastine, vincristine,mitoazitrone, oxaliplatin, procarbazine streptocin, taxol or paclitaxel,taxotere, analogs/congeners, derivatives of such compounds, andcombinations thereof.

Exemplary decongestants include, but are not limited to, epinephrine,pseudoephedrine, oxymetazoline, phenylephrine, tetrahydrozolidine, andxylometazoline. Mucolytics that may be used include, but are not limitedto, acetylcysteine, dornase alpha, and guaifenesin. Antihistamines suchas azelastine, diphenhydramine, and loratidine may also be used.

In those instances where it is desirable to remove water from tissue,e.g., to remove fluid from polyps or edematous tissue, a hyperosmolaragent may be employed. Suitable hyperosmolar agents include, but are notlimited to, furosemide, sodium chloride gel, or other salt preparationsthat draw water from tissue or substances that directly or indirectlychange the osmolar content of the mucous layer.

Where sustained release or delayed release of the therapeutic agent isdesirable, a release agent modifier or other hydrophilic and/orhydrophobic material such as hydroxypropylcellulose, poly(ethyleneoxide), polylactic acid hydroxypropyl methylcellulose, ethylcellulose,cellulosic polymers, acrylic polymers, fats, waxes, lipids,polysaccharides, and mixtures thereof may also be present in the medicalsealant. The therapeutic agent may also be contained within polymericmicrospheres to further delay and/or sustain release of the agent.

The medical sealant may also, if desired include such additives andflavorant where appropriate. Any known flavorant may be used. Examplesinclude anise oil, cinnamon oil, cocoa, menthol, orange or other citrusoils, peppermint oil, spearmint oil, vanillin, fruit flavors andessences, herbal aromatics such as clove oil, sage oil, cassia oil, andthe like. The sealant may also include a colorant such as FD & C Red No.3, FD & C Red No. 20, FD & C Yellow No. 6, FD & C Blue No. 2, D & CGreen No. 5, D & C Orange N. 4, D & C Red No. 8, caramel, titaniumdioxide, fruit or vegetable colorants such as beet powder, orbeta-carotene, turmeric, paprika and others known in the art. Thecolorant is included to provide visual notification of the presence ofthe sealant.

Although specific embodiments have been illustrated and described hereinfor purposes of description of the preferred embodiment, it will beappreciated by those of ordinary skill in the art that a wide variety ofalternate and/or equivalent implementations calculated to achieve thesame purposes may be substituted for the specific embodiments shown anddescribed without departing from the scope of the present invention.Those with skill in the chemical, mechanical, biomedical; andbiomaterials arts will readily appreciate that the present invention maybe implemented in a very wide variety of embodiments. This applicationis intended to cover any adaptations or variations of the preferredembodiments discussed herein. Therefore, it is manifestly intended thatthis invention be limited only by the claims and the equivalentsthereof.

1: A polymeric film-forming medical sealant comprising a film, gel,sheet, sponge or powder applied to the tonsils, adenoids or paranasalsinus of a mammal other than a human, wherein the sealant performs atleast one of the following functions, a) inhibiting the colonization ofbacteria, b) inhibiting the binding of bacteria to tissue, c) reducingtissue morbidity, d) hemostasis, e) coating and protection of tissueduring healing, f) promoting healing, and g) reducing pain. 2: Apolymeric film-forming medical sealant according to claim 1 wherein saidsealant inhibits the colonization of bacteria. 3: A polymericfilm-forming medical sealant according to claim 1 wherein said sealantinhibits the binding of bacteria to tissue. 4: A polymeric film-formingmedical sealant according to claim 1 wherein said sealant reduces tissuemorbidity in tissue to which it is applied. 5: A polymeric film-formingmedical sealant according to claim 1 wherein said sealant reducesbleeding. 6: A polymeric film-forming medical sealant according to claim1 wherein said sealant coats and protects tissue during healing. 7: Apolymeric film-forming medical sealant according to claim 1 wherein theapplication of said sealant reduces pain in tissue to which it isapplied during treatment or postoperative healing.
 8. (canceled) 9: Apolymeric film-forming medical sealant according to claim 1 wherein saidsealant hardens or crosslinks to form a semi-pliable barrier uponapplication. 10: A polymeric film-forming medical sealant according toclaim 1 wherein said sealant has a residence time of at least about oneday. 11: A polymeric film-forming medical sealant according to claim 1wherein said sealant has a residence time of at least about one week.12: A polymeric film-forming medical sealant according to claim 1wherein said sealant has a residence time of at least about one month.13: A polymeric film-forming medical sealant according to claim 1wherein said sealant is applied as an atomized powder or atomizedliquid.
 14. (canceled) 15: A polymeric film-forming medical sealantaccording to claim 8 wherein said sealant comprises a polyethyleneglycol. 16: A polymeric film-forming medical sealant according to claim1 wherein said sealant comprises a silk or silk-elastin polymercrosslinked with a crosslinking agent selected from an aldehyde, athiol, or a chitosan. 17: A polymeric film-forming medical sealantaccording to claim 1 wherein said sealant is crosslinked with analdehyde selected from formaldehyde and glutaraldehyde. 18: A polymericfilm-forming medical sealant according to claim 1 further including atleast one therapeutic agent selected from the group consisting ofanalgesics, antihistamines, anti-infective agents, anti-fungal agents,biostatic compositions, anti-inflammatory agents, anti-cholinergics,anti-neoplastic agents, cytokines, decongestants, vitamins, peptides,proteins, nucleic acids, immunosuppressors, vasoconstrictors andmixtures thereof. 19: A polymeric film-forming medical sealant accordingto claim 1 further including a blood product. 20: A method of treatmentfor conditions of the tonsils, adenoids or paranasal sinus of a mammalother than a human, which method comprises the step of providing atleast one polymeric film-forming medical sealant according to claim 1,and applying it to the tonsils, adenoids, paranasal sinus or adjacenttissue. 21-23. (canceled) 24: A polymeric film-forming medical sealantaccording to claim 1 wherein said sealant has a colorant that providesvisual confirmation of the sealant present at a surgical site. 25: Apolymeric film-forming medical sealant according to claim 1 wherein thesealant is a synthetic polymer. 26: A polymeric film-forming medicalsealant according to claim 1 wherein the sealant is a natural polymer.27: A polymeric film-forming medical sealant according to claim 1wherein the sealant comprises a crosslinking material. 28: A polymericfilm-forming medical sealant according to claim 1 wherein the sealantcomprises a poly(lactide), poly(glycolide), poly(lactide-co-glycolide),poly(lactic acid), poly(glycolic acid), polycaprolactone, polyamide,poly(malic acid), polyanhydride, polyamino acid, polyorthoester,polyetherester, polycyanoacrylate, polyphosphazine, polyphosphoester,polyesteramide, polydiozanone, polyacetal, polyketal, polycarbonate,polyurethane, polyvinyl pyrrolidone, polyhydroxybutyrate,polyhydoxyvalerate, polyalkylene oxalate, polyalkylene succinate, or acopolymer, terpolymer, blend, or mixture thereof. 29: A polymericfilm-forming medical sealant according to claim 1 wherein the sealantcomprises hydroxypropylcellulose, poly(ethylene oxide), polylactic acid,hydroxypropyl methylcellulose, ethylcellulose, a cellulosic polymer, anacrylic polymer, a fat, a wax, a lipid, a polysaccharide, or mixturethereof.